We continue our studies using the in vivo kinetic approach to define the metabolic pathways of plasma VLDL metabolism in man. Factors affecting the formation and removal of remnant VLDL particles and the sites of their catabolism are examined. These pathways are investigated in adult onset diabetic subjects to reveal abnormalities in the metabolic fate of plasma VLDL which may or may not be apparent from measurement of fasting plasma lipid levels. We assess the effects of diabetic control upon these abnormalities. The in vivo studies are extended to examine in isolated adipocytes, the subcellular steps which mediate the synthesis of the enzyme lipoprotein lipase and the defects which may result in the insulin resistance of the spontaneously obese aged rat. Specific changes in polyribosomal activities and phosphorylation or in lipoprotein lipase mRNA coinciding with the effects of the hormone on fat cells are explored. We also evaluate the importance of calcium ions in insulin action and their participation in the evolution of insulin resistance. The investigation is a multi-level approach to define the pathophysiology of the lipid disorder in diabetes.